Recent evidence suggests that in myocardium the sodium-calcium exchange mechanism is operative during reperfusion states and that the exchange, and the potential ramifications of cellular calcium loading, are critically dependent on the transmembrane sodium gradient. The purpose of this proposal is to investigate the hypothesis by continuously monitoring intracellular sodium activity by the use of ion selective electrodes, in isolated myocardium, during two different types of reperfusion experiments. The first experiments will investigate oxygen deprivation followed by reoxygenation, and the second, calcium deprivation followed by calcium reperfusion. Furthermore, the proposed experiments seek to define the factors which alter the transmembrane sodium activity gradient during these deprivation periods and especially during reperfusion. The intracellular sodium activity, and hence the transmembrane sodium gradient, will be monitored by sodium ion selective electrodes during these experiments in quiescent, isolated superfused ferret myocardium. In these experiments the relationship between changes in the transmembrane sodium gradient and rest force will be analyzed. The long term objective will be divided into three parts. The specific aim of part one will be to define and assess factors which influence intracellular sodium activity during hypoxia. These experiments are designed to ascertain how intracellular sodium activity loading and unloading may be accomplished during hypoxia. The purpose of part two will be to define the course of change in intracellular sodium activity during reoxygenation and to define the factors and methods which alter this course. During oxygen reperfusion the experiments are designed to attempt modification of the transmembrane sodium gradient by intervening at reperfusion. Part three is designed to assay the transmembrane sodium gradient during a short period of calcium free perfusion and subsequent calcium reperfusion, the calcium paradox. The factors and methods which alter the intracellular sodium activity during the calcium free period, and especially reperfusion will be defined.